The aim of this study was to investigate the curative effect of Zeng Ye decoction on primary Sjögren's syndrome (pSS) and further explore its underlying mechanism involving aquaporin (AQP)‑1 and AQP‑5. The pSS model was established based on the immune induction method, and the saliva flow, submandibular gland index, morphological structures of salivary glands, and AQP‑1 and AQP‑5 protein expression levels in the salivary glands were determined. The saliva flow and the submandibular gland index were significantly reduced in the model group (P<0.01, compared with those in the control group), and significantly increased following interferon (IFN), Zeng Ye decoction extraction (ZYE) and Zeng Ye decoction (ZY) treatment (P<0.01, compared with those of the model group). Submandibular gland atrophy, fibrous tissue hyperplasia and multiple focal lymphocytic infiltration were observed in the model group and were attenuated when subjected to IFN, ZYE and ZY treatment. The AQP‑1 and AQP‑5 expression levels increased following IFN, ZYE and ZY treatment (P<0.01, compared with those of the model group), particularly in the ZYE‑35 group. This result indicated that ZYE had a significant protective effect on pSS via upregulation of the expression levels of AQP‑1 and/or AQP‑5. However, the AQP‑1 expression levels increased and the AQP‑5 expression levels decreased in the model groups compared with those in the control group, which indicated different regulatory pathways of the salivary gland damage on the basis of AQP‑1 and AQP‑5. This study provided a significant reference for the prevention and treatment of pSS.